Cooperative Recruitment of FtsW to the Division Site of Bacillus subtilis

Gamba, Pamela; Hamoen, Leendert W.; Daniel, Richard A.

doi:10.3389/fmicb.2016.01808

Cited by 19 publications

(12 citation statements)

References 40 publications

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“…subtilis (35, 36, 39, 43). Depletion of FtsW in these organisms leads to a block in cell division and formation of elongated cells (36, 37). All our attempts to delete the ftsW1 gene in L.…”

Section: Resultsmentioning

confidence: 99%

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Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in Listeria monocytogenes

Rismondo

Halbedel

Gründling

2019

mBio

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Rod-shaped bacteria have two modes of peptidoglycan synthesis: lateral synthesis and synthesis at the cell division site. These two processes are controlled by two macromolecular protein complexes, the elongasome and divisome. Recently, it has been shown that the Bacillus subtilis RodA protein, which forms part of the elongasome, has peptidoglycan glycosyltransferase activity. The cell division-specific RodA homolog FtsW fulfils a similar role at the divisome. The human pathogen Listeria monocytogenes carries genes that encode up to six FtsW/RodA homologs; however, their functions have not yet been investigated. Analysis of deletion and depletion strains led to the identification of the essential cell division-specific FtsW protein, FtsW1. Interestingly, L. monocytogenes carries a gene that encodes a second FtsW protein, FtsW2, which can compensate for the lack of FtsW1, when expressed from an inducible promoter. L. monocytogenes also possesses three RodA homologs, RodA1, RodA2, and RodA3, and their combined absence is lethal. Cells of a rodA1 rodA3 double mutant are shorter and have increased antibiotic and lysozyme sensitivity, probably due to a weakened cell wall. Results from promoter activity assays revealed that expression of rodA3 and ftsW2 is induced in the presence of antibiotics targeting penicillin binding proteins. Consistent with this, a rodA3 mutant was more susceptible to the β-lactam antibiotic cefuroxime. Interestingly, overexpression of RodA3 also led to increased cefuroxime sensitivity. Our study highlights that L. monocytogenes genes encode a multitude of functional FtsW and RodA enzymes to produce its rigid cell wall and that their expression needs to be tightly regulated to maintain growth, cell division, and antibiotic resistance. IMPORTANCE The human pathogen Listeria monocytogenes is usually treated with high doses of β-lactam antibiotics, often combined with gentamicin. However, these antibiotics only act bacteriostatically on L. monocytogenes, and the immune system is needed to clear the infection. Therefore, individuals with a compromised immune system are at risk to develop a severe form of Listeria infection, which can be fatal in up to 30% of cases. The development of new strategies to treat Listeria infections is necessary. Here we show that the expression of some of the FtsW and RodA enzymes of L. monocytogenes is induced by the presence of β-lactam antibiotics, and the combined absence of these enzymes makes bacteria more susceptible to this class of antibiotics. The development of antimicrobial agents that inhibit the activity or production of FtsW and RodA enzymes might therefore help to improve the treatment of Listeria infections and thereby lead to a reduction in mortality.

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Section: Resultsmentioning

confidence: 99%

“…subtilis (34). In contrast, FtsW is essential for cell division, and cells depleted for FtsW grow as long filaments (35–37). B.…”

Section: Introductionmentioning

confidence: 99%

Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in Listeria monocytogenes

Rismondo

Halbedel

Gründling

2019

mBio

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“…The earlier timing of FtsL and FtsB localization, the partial dependency of FtsQ localization on FtsB and FtsL and the interdependency of FtsB and FtsL localization (61,62) implies that these proteins may all slowly accumulate at midcell and help stabilize each other there. There is precedent in B. subtilis for early septal factors to be dependent on later factors for stabilization to the septum (63).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Conserved and Novel Septal Factors in Mycobacterium smegmatis

et al. 2018

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Septation in bacteria requires coordinated regulation of cell wall biosynthesis and hydrolysis enzymes so that new septal cross-wall can be appropriately constructed without compromising the integrity of the existing cell wall. Bacteria with different modes of growth and different types of cell wall require different regulators to mediate cell growth and division processes. Mycobacteria have both a cell wall structure and a mode of growth that are distinct from well-studied model organisms and use several different regulatory mechanisms. Here, using , we identify and characterize homologs of the conserved cell division regulators FtsL and FtsB, and show that they appear to function similarly to their homologs in We identify a number of previously undescribed septally localized factors which could be involved in cell wall regulation. One of these, SepIVA, has a DivIVA domain, is required for mycobacterial septation, and is localized to the septum and the intracellular membrane domain. We propose that SepIVA is a regulator of cell wall precursor enzymes that contribute to construction of the septal cross-wall, similar to the putative elongation function of the other mycobacterial DivIVA homolog, Wag31. The enzymes that build bacterial cell walls are essential for cell survival but can cause cell lysis if misregulated; thus, their regulators are also essential. The number and nature of these regulators is likely to vary in bacteria that grow in different ways. The mycobacteria are a genus that have a cell wall whose composition and construction vary greatly from those of well-studied model organisms. In this work, we identify and characterize some of the proteins that regulate the mycobacterial cell wall. We find that some of these regulators appear to be functionally conserved with their structural homologs in evolutionarily distant species such as , but other proteins have critical regulatory functions that may be unique to the actinomycetes.

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“…These proteins do not have clear catalytic domains and it is assumed that they play a structural role and somehow regulate the recruitment of late cell division proteins to the Z-ring. In B. subtilis , this recruitment is a strongly cooperative process and the absence of one of the late proteins (except for the non-essential protein DivIB) inhibits assembly of all late cell division proteins 16 , 17 . For a recent review on bacterial cell division see e.g.…”

Section: Introductionmentioning

confidence: 99%

Free SepF interferes with recruitment of late cell division proteins

Gao

Wenzel

Jonker

et al. 2017

Sci Rep

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The conserved cell division protein SepF aligns polymers of FtsZ, the key cell division protein in bacteria, during synthesis of the (Fts)Z-ring at midcell, the first stage in cytokinesis. In addition, SepF acts as a membrane anchor for the Z-ring. Recently, it was shown that SepF overexpression in Mycobacterium smegmatis blocks cell division. Why this is the case is not known. Surprisingly, we found in Bacillus subtilis that SepF overproduction does not interfere with Z-ring assembly, but instead blocks assembly of late division proteins responsible for septum synthesis. Transposon mutagenesis suggested that SepF overproduction suppresses the essential WalRK two-component system, which stimulates expression of ftsZ. Indeed, it emerged that SepF overproduction impairs normal WalK localization. However, transcriptome analysis showed that the WalRK activity was in fact not reduced in SepF overexpressing cells. Further experiments indicated that SepF competes with EzrA and FtsA for binding to FtsZ, and that binding of extra SepF by FtsZ alleviates the cell division defect. This may explain why activation of WalRK in the transposon mutant, which increases ftsZ expression, counteracts the division defect. In conclusion, our data shows that an imbalance in early cell division proteins can interfere with recruitment of late cell division proteins.

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Cooperative Recruitment of FtsW to the Division Site of Bacillus subtilis

Cited by 19 publications

References 40 publications

Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in Listeria monocytogenes

Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in Listeria monocytogenes

Characterization of Conserved and Novel Septal Factors in Mycobacterium smegmatis

Free SepF interferes with recruitment of late cell division proteins

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